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Long non-coding RNAs (lncRNAs) are non-coding RNAs that are >200 nucleotides in length. Recent studies have identified a number of lncRNAs with critical roles in various biological processes including tumorigenesis. Zinc finger antisense 1 (ZFAS1) is a lncRNA that has recently been reported to be involved in the progression of several human cancers. However, the biological function of ZFAS1 in breast cancer remains to be elucidated. In order to determine the effect of ZFAS1 in breast cancer cells, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to measure ZFAS1 expression in cells from breast cancer cell lines. In addition, gain-of-function experiments were performed in vitro to investigate the biological role of ZFAS1. The results revealed that ZFAS1 expression was significantly downregulated in breast cancer cell lines when compared with the levels in controls. In vitro experiments also demonstrated that ZFAS1 overexpression significantly suppressed cell proliferation by causing cell cycle arrest and inducing apoptosis in breast cancer cells. Further functional assays indicated that ZFAS1 overexpression inhibited cell migration and invasion by regulating epithelial-mesenchymal transition. These findings indicated that the lncRNA ZFAS1 may be a tumor suppressor in breast cancer, and thus, may serve as a potential therapeutic target for patients with breast cancer.

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SUMMARY Aberrant expression of nuclear transporters and deregulated subcellular localization of their cargo proteins are emerging as drivers and therapeutic targets of cancer. Here, we present evidence that the nuclear exporter exportin-6 and its cargo profilin-1 constitute a functionally important and frequently deregulated axis in cancer. Exportin-6 upregulation occurs in numerous cancer types and is associated with poor patient survival. Reducing exportin-6 level in breast cancer cells triggers antitumor effects by accumulating nuclear profilin-1. Mechanistically, nuclear profilin-1 interacts with eleven-nineteen-leukemia protein (ENL) within the super elongation complex (SEC) and inhibits the ability of the SEC to drive transcription of numerous pro-cancer genes including MYC . XPO6 and MYC are positively correlated across diverse cancer types including breast cancer. Therapeutically, exportin-6 loss sensitizes breast cancer cells to the bromodomain and extra-terminal (BET) inhibitor JQ1. Thus, exportin-6 upregulation is a previously unrecognized cancer driver event by spatially inhibiting nuclear profilin-1 as a tumor suppressor.

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This work describes a novel methodology for unequivocal identification of chemical constituents in Zhimu-Baihe herb-pair (ZMBHHP). Compounds were removed from ZMBHHP by ultrasonic extraction with 70% ethanol, and then analyzed by fast high-performance liquid chromatography (HPLC) coupled with time-of-flight mass spectrometry (TOFMS). The accurate-mass capability of the TOF analyzer allowed reliable confirmation of the identity of the detected compounds, normally with mass errors below 3 ppm in routine analysis. This mass accuracy was sufficient to verify the elemental compositions of the chemical constituents in ZMBHHP. With dynamic adjustment of fragmentor voltage in TOFMS, an efficient ion transmission was achieved to obtain the best sensitivity and abundant fragmentation. By accurate mass measurements for each molecular ion and subsequent fragment ions, a reliable identification and differentiation of 24 saponins, 3 xanthones, 1 anthraquinone and 2 alkaloids was described here, including four groups of isomers. It is concluded that this fast and sensitive HPLC/ESI-TOFMS technique is powerful in qualitative analysis of complex herbal medicines in terms of sensitivity, selectivity, resolving power, time savings and lower solvent consumption. Furthermore, the data gathered in this study may be helpful for understanding the synergistic nature of this herb pair in traditional Chinese medicine (TCM) and further pharmacokinetic studies of ZMBHHP.